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The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate immune responses

Lookup NU author(s): Professor Colin Brooks


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NKR-P1B is a homodimeric type II transmembrane C-type lectinlike receptor that inhibits natural killer (NK) cell function upon interaction with its cognate C-type lectin-related ligand, Clr-b. The NKR-P1B: Clr-b interaction represents a major histocompatibility complex class I (MHC-I)-independent missing-self recognition system that monitors cellular Clr-b levels. We have generated NKR-P1B(B6)-deficient (Nkrp1b(-/-)) mice to study the role of NKR-P1B in NK cell development and function in vivo. NK cell inhibition by Clr-b is abolished in Nkrp1b(-/-) mice, confirming the inhibitory nature of NKR-P1B(B6). Inhibitory receptors also promote NK cell tolerance and responsiveness to stimulation; hence, NKcells expressingNKR-P1B(B6) and Ly49C/I display augmented responsiveness to activating signals vs NK cells expressing either or none of the receptors. In addition, Nkrp1b(-/-) mice are defective in rejecting cells lacking Clr-b, supporting a role for NKR-P1B(B6) in MHC-I-independent missing-self recognition of Clr-b in vivo. In contrast, MHC-I-dependent missing-self recognition is preserved in Nkrp1b(-/-) mice. Interestingly, spontaneous myc-induced B lymphoma cells may selectively use NKR-P1B: Clr-b interactions to escape immune surveillance by wild-type, but not Nkrp1b(-/-), NK cells. These data provide direct genetic evidence of a role for NKR-P1B in NK cell tolerance and MHC-I-independent missing-self recognition.

Publication metadata

Author(s): Rahim MMA, Chen P, Mottashed AN, Mahmoud AB, Thomas MJ, Zhu QZ, Brooks CG, Kartsogiannis V, Gillespie MT, Carlyle JR, Makrigiannis AP

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2015

Volume: 125

Issue: 14

Pages: 2217-2227

Print publication date: 02/04/2015

Online publication date: 22/01/2015

Acceptance date: 06/01/2015

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2014-02-556142

PubMed id: 25612621


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